The Hair Follicle and the Hair Growth Cycle
The hair follicle is composed of an epithelial component, the matrix and outer root sheath enclosing the hair shaft and a dermal component, the dermal papilla within the bulb. Hair growth is effected by the division of the hair follicle basal cells and in the mammal, this is cyclical. Three distinct stages of hair growth can be identified, namely:
i. an active stage known as anagen, during which the hair follicle penetrates deep into the dermis with the cells of the bulb dividing rapidly and differentiating to form the hair,
ii. a regressive stage known as catagen, which is heralded by the cessation of mitosis, and during which the follicle regresses upwards through the dermis and hair growth ceases, and
iii. a resting stage known as telogen, in which the regressed follicle contains a small secondary germ with an underlying ball of tightly packed dermal papilla cells.
The initiation of a new anagen stage is revealed by rapid proliferation in the germ, expansion of the dermal papilla and elaboration of basement membrane components. The hair cycle is then repeated many times until, as a consequence of the onset of male pattern baldness, most of the hair follicles spend an increasing proportion of their time in the telogen stage, and the hairs produced become finer, shorter, and less visible; this is known as terminal to vellus transformation.
Loss of hair on the human head, particularly that which results in male pattern baldness, is a natural process often associated with advancing age. Baldness occurring in young people, particularly men, can give the impression that age is advancing faster than it really is.
Baldness can also result from a disorder of the skin known as Alopecia areata.
Since time immemorial, man has striven to maintain the appearance of youth with potions and lotions to preserve skin condition and also to reverse the natural ageing process. This has applied also to hair loss, with the result that many hair restorers, hair lotions and the like have been applied to the scalp in an attempt to slow or arrest hair loss or to increase hair growth.
In order to determine whether any substance at least has the potential to restore or otherwise enhance hair growth on the scalp, or even to retard growth, it is first necessary to carry out clinical tests involving applying the substance to the skin of a test animal, for example the rat, or to human volunteers. Although ultimately, the results of in vivo clinical tests are required to support patenting and/or commercial exploitation, such tests are time consuming and costly to perform. Accordingly, there exists a need for an in vitro screening test to determine rapidly whether or not a substance at least has the potential for enhancing or retarding hair growth.
Attempts have in the past been made to isolate hair follicles and then to cultivate them to maintain viability, in order to use them to determine the activity of potential hair growth substances, by studying their biochemical behaviour following contact with such substances. An example of this is referred to by Rogers et al., in a paper entitled "Cultivation of Murine Hair Follicles as Organoids in a Collagen Matrix", published in the Journal of Investigative Dermatology, 89, No. 4, (1987), 369-379, who described the isolation and cultivation of functionally intact mouse hair follicles. In this technique, follicles were isolated by collagenase digestion of dermis from five-day-old mice and purified by differential centrifugation and filtration. Purified follicles were then cultured in a collagen matrix.
In a further technique described by Buhl et al. in a paper entitled "Minoxidil stimulates mouse vibrissae follicles in organ culture", published in the Journal of Investigative Dermatology, 92, No. 3, (1989), 315-320, a method of testing the hair growth stimulating drug, Minoxidil, is described. Here, whisker follicles were dissected from three-day-old mice and cultured in Dulbecco's Modified Eagles medium, with added fetal bovine serum and Gentamicin, with or without Minoxidil, in the presence of 10% CO.sub.2 at 37.degree. C., and follicle function was assessed by measuring the uptake of radiolabelled cysteine, glycine and or thymidine, by quantifying changes in follicle-hair shaft length and with histology. The authors reported that culture of control follicles (without Minoxidil) showed macroscopic changes including kinking of the hair shafts and bending of the follicles. Furthermore, necrosis was evident in the differentiating epithelial elements forming the cuticle, cortex and inner root sheath. Although culture of similar follicles in the presence of Minoxidil reduced or eliminated these abnormalities and caused them to grow longer than controls over a 3 day period, it is clear that the dissection technique originally employed (using jeweller's forceps operating on separated whisker pads) caused sufficient damage to the individual whisker follicles to detract from their usefulness in testing potential hair growth promoters. Accordingly, there remains a need for a more delicate yet productive technique for removing hair follicles from the skin in an undamaged state, such that they can then reliably be used to assess, by culture while in a fully viable state, the potential activity of substances for promoting or retarding hair growth promoters.